The proposal intends to determine whether intravascular volume changes occur in selected regions of the capacitance vasculature and whether cardiac output is altered subsequent to the regional volume changes during various interventions in intact organisms. These aims are consistent with the applicant's long term objective to examine the influence of hemodynamic alterations in the capacitance vasculature on overall circulatory performance. Such an examination is important since many pathologic conditions and therapeutic interventions may influence circulatory function by means of effects on the capacitance circulation. This proposal will examine the influence of selective adrenergic and cholingeric receptor stimulation; administration of ouabain, verapamil, nitroglycerin, and naloxone; and the initiation of autonomic reflex phenomena on regional capacitance volume in intact anesthetized dogs, conscious dogs, and normal human subjects. Splanchnic, limb, and pulmonary blood volume changes will be measured by quantitative radionuclide imaging and plethysmography. It is expected that the total peripheral volume response will be determined mostly by the splanchnic volume response. Thus, the extent to which splanchnic volume changes are due to direct effects on the splanchnic capacitance vessels as opposed to changes in splanchnic inflow and right atrial pressure will be determined. Furthermore, whether the splanchnic volume response causes a change in cardiac output and the extent to which this influence is modified by changes in systemic arterial pressure, cardiac contractility, and heart rate will be ascertained. Finally, whether pulmonary blood volume is changed subseqent to the splanchnic response or subsequent to direct actions of the interventions on the pulmonary circulation will be determined. Thus, these studies should demonstrate the extent to which capacitance volume changes influence circulatory function during various physiologic and therapeutic interventions.